A large number of investigators at Virginia Commonwealth University (VCU) have made significant contributions to our knowledge of drugs of abuse and related phenomena during the past two decades. The interests of these researchers encompass behavioral, pharmacokinetic, neurochemical, and pharmacological characterization of all classes of abused drugs. While there have always been active collaborations among these investigators, the drug abuse research effort at VCU has been enhanced by the creation of the NIDA Center on Drug Abuse Research. The primary objective of the Center is to foster interdisciplinary research on drug abuse at VCU. The Center will continue to provide a mechanism for bringing together scientists from many different disciplines (pharmacology, toxicology, physiology, histology, biostatistics, neurology, medicinal chemistry, microbiology, pediatrics, substance abuse medicine, etc.) who have had the opportunity to share information and ideas regarding abused drugs. Another major contribution has been to facilitate the training and development of young scientists in drug abuse research. Our success in stimulating collaborative research as well as in recruiting young investigators into drug abuse research is reflected in the growth of the Center which is composed of a core and eight research projects. The role of the Core is to provide program management and facilitate interaction and cooperation among the participants through its administrative, drug synthesis, instrumentation and statistical components. The objective of Project 1 is to test the dopamine hypothesis of the mechanism of action of cocaine through structure-activity relationship studies in rats. Project 2 is designed to verify that there is an increased incidence of apnea in infants exposed in utero to drugs of abuse and to devise effective treatment strategies. The objective of Project 3 is to understand in a comprehensive manner how cocaine affects the cerebral circulation and microvascular function. The evaluation of the functional role of central nicotine receptors will be carried out in Project 4. The hypothesis to be tested is that nicotine agonists and antagonists act through two distinct receptor systems which have not yet been fully characterized. Studies will be conducted in both normal and brain-injured adults as well as in neonatal animals. The impact of opioid exposure on the fetus during pregnancy has not been fully explored. Therefore, the effects of in utero methadone exposure on brain neurochemistry will continue to be evaluated in Project 5. The growing concern as to when and how pain in newborns should be treated forms the basis of Project 6. The emphasis will be placed upon the assessment of the development of opioid tolerance and dependence in neonatal rats. Project 7 will be devoted to the cloning of cannabinoid receptors and subsequent pharmacological characterization in order to establish the functional role of these receptor in the central nervous system. Finally, the objective of Project 8 will be the elucidation of the antinociceptive mechanism(s) of cannabinoids with particular emphasis on second messenger systems.